LOCUS       NM_178645               2355 bp    mRNA    linear   ROD 03-JUN-2024
DEFINITION  Mus musculus bleomycin hydrolase (Blmh), mRNA.
ACCESSION   NM_178645
VERSION     NM_178645.4
KEYWORDS    RefSeq; RefSeq Select.
SOURCE      Mus musculus (house mouse)
  ORGANISM  Mus musculus
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
            Muroidea; Muridae; Murinae; Mus; Mus.
REFERENCE   1  (bases 1 to 2355)
  AUTHORS   Witucki,L., Borowczyk,K., Suszynska-Zajczyk,J., Warzych,E.,
            Pawlak,P. and Jakubowski,H.
  TITLE     Deletion of the Homocysteine Thiolactone Detoxifying Enzyme
            Bleomycin Hydrolase, in Mice, Causes Memory and Neurological
            Deficits and Worsens Alzheimer's Disease-Related Behavioral and
            Biochemical Traits in the 5xFAD Model of Alzheimer's Disease
  JOURNAL   J Alzheimers Dis 95 (4), 1735-1755 (2023)
   PUBMED   37718819
  REMARK    GeneRIF: Deletion of the Homocysteine Thiolactone Detoxifying
            Enzyme Bleomycin Hydrolase, in Mice, Causes Memory and Neurological
            Deficits and Worsens Alzheimer's Disease-Related Behavioral and
            Biochemical Traits in the 5xFAD Model of Alzheimer's Disease.
REFERENCE   2  (bases 1 to 2355)
  AUTHORS   Thyssen,J.P., Jakasa,I., Riethmuller,C., Schon,M.P., Braun,A.,
            Haftek,M., Fallon,P.G., Wroblewski,J., Jakubowski,H., Eckhart,L.,
            Declercq,W., Koppes,S., Engebretsen,K.A., Bonefeld,C., Irvine,A.D.,
            Keita-Alassane,S., Simon,M., Kawasaki,H., Kubo,A., Amagai,M.,
            Matsui,T. and Kezic,S.
  TITLE     Filaggrin Expression and Processing Deficiencies Impair Corneocyte
            Surface Texture and Stiffness in Mice
  JOURNAL   J Invest Dermatol 140 (3), 615-623 (2020)
   PUBMED   31479664
REFERENCE   3  (bases 1 to 2355)
  AUTHORS   Suszynska-Zajczyk,J., Utyro,O. and Jakubowski,H.
  TITLE     Methionine-induced hyperhomocysteinemia and bleomycin hydrolase
            deficiency alter the expression of mouse kidney proteins involved
            in renal disease
  JOURNAL   Mol Genet Metab 112 (4), 339-346 (2014)
   PUBMED   24913063
  REMARK    GeneRIF: Blmh interacts with diverse cellular
            processes--lipoprotein, amino acid and protein, carbohydrate, and
            energy metabolisms, detoxification, antioxidant defenses--that are
            essential for normal kidney homeostasis.
REFERENCE   4  (bases 1 to 2355)
  AUTHORS   Borowczyk,K., Tisonczyk,J. and Jakubowski,H.
  TITLE     Metabolism and neurotoxicity of homocysteine thiolactone in mice:
            protective role of bleomycin hydrolase
  JOURNAL   Amino Acids 43 (3), 1339-1348 (2012)
   PUBMED   22227865
  REMARK    GeneRIF: Bleomycin hydrolase protects against neurodegeneration
            associated with elevated homocysteine thiolactone levels in
            hyperhomocysteinemia and Alzheimer's disease.
REFERENCE   5  (bases 1 to 2355)
  AUTHORS   Towne,C.F., York,I.A., Watkin,L.B., Lazo,J.S. and Rock,K.L.
  TITLE     Analysis of the role of bleomycin hydrolase in antigen presentation
            and the generation of CD8 T cell responses
  JOURNAL   J Immunol 178 (11), 6923-6930 (2007)
   PUBMED   17513741
  REMARK    GeneRIF: BH does not play a major role either in generating or
            destroying class I major histocompatibility antigen (MHC)-presented
            peptides that bind to the MHC in living cells. These results point
            to redundant functions between peptidases.
REFERENCE   6  (bases 1 to 2355)
  AUTHORS   Montoya,S.E., Thiels,E., Card,J.P. and Lazo,J.S.
  TITLE     Astrogliosis and behavioral changes in mice lacking the neutral
            cysteine protease bleomycin hydrolase
  JOURNAL   Neuroscience 146 (3), 890-900 (2007)
   PUBMED   17391860
REFERENCE   7  (bases 1 to 2355)
  AUTHORS   Haston,C.K., Wang,M., Dejournett,R.E., Zhou,X., Ni,D., Gu,X.,
            King,T.M., Weil,M.M., Newman,R.A., Amos,C.I. and Travis,E.L.
  TITLE     Bleomycin hydrolase and a genetic locus within the MHC affect risk
            for pulmonary fibrosis in mice
  JOURNAL   Hum Mol Genet 11 (16), 1855-1863 (2002)
   PUBMED   12140188
  REMARK    GeneRIF: bleomycin hydrolase functions as an MHC class I
            epitope-processing protease
REFERENCE   8  (bases 1 to 2355)
  AUTHORS   Stoltze,L., Schirle,M., Schwarz,G., Schroter,C., Thompson,M.W.,
            Hersh,L.B., Kalbacher,H., Stevanovic,S., Rammensee,H.G. and
            Schild,H.
  TITLE     Two new proteases in the MHC class I processing pathway
  JOURNAL   Nat Immunol 1 (5), 413-418 (2000)
   PUBMED   11062501
REFERENCE   9  (bases 1 to 2355)
  AUTHORS   Schwartz,D.R., Homanics,G.E., Hoyt,D.G., Klein,E., Abernethy,J. and
            Lazo,J.S.
  TITLE     The neutral cysteine protease bleomycin hydrolase is essential for
            epidermal integrity and bleomycin resistance
  JOURNAL   Proc Natl Acad Sci U S A 96 (8), 4680-4685 (1999)
   PUBMED   10200322
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BY087076.1, AK049461.1 and
            BY643607.1.
            
            On Jan 13, 2010 this sequence version replaced NM_178645.3.
            
            Summary: The encoded protein is a cytoplasmic cysteine peptidase
            involved in inactivation of bleomycin, a glycopeptide which is a
            component of combination chemotherapy regimens for cancer. This
            encoded enzyme is highly conserved, and it contains the signature
            active site residues of cysteine protease papain superfamily
            enzymes. It is postulated that this enzyme has protective effects
            against bleomycin-induced pulmonary fibrosis and bleomycin tumor
            resistance. [provided by RefSeq, Jan 2010].
            
            ##Evidence-Data-START##
            Transcript exon combination :: AK049461.1, BC027403.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMN00849374, SAMN00849375
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-88                BY087076.1         1-88
            89-1050             AK049461.1         1-962
            1051-2344           AK049461.1         964-2257
            2345-2355           BY643607.1         391-401
FEATURES             Location/Qualifiers
     source          1..2355
                     /organism="Mus musculus"
                     /mol_type="mRNA"
                     /strain="C57BL/6"
                     /db_xref="taxon:10090"
                     /chromosome="11"
                     /map="11 46.16 cM"
     gene            1..2355
                     /gene="Blmh"
                     /gene_synonym="Bh; Bmh"
                     /note="bleomycin hydrolase"
                     /db_xref="GeneID:104184"
                     /db_xref="MGI:MGI:1345186"
     exon            1..238
                     /gene="Blmh"
                     /gene_synonym="Bh; Bmh"
                     /inference="alignment:Splign:2.1.0"
     CDS             226..1593
                     /gene="Blmh"
                     /gene_synonym="Bh; Bmh"
                     /EC_number="3.4.22.40"
                     /note="BLM hydrolase"
                     /codon_start=1
                     /product="bleomycin hydrolase"
                     /protein_id="NP_848760.1"
                     /db_xref="CCDS:CCDS25073.1"
                     /db_xref="GeneID:104184"
                     /db_xref="MGI:MGI:1345186"
                     /translation="MNNAGLNSEKVSALIQKLNSDPQFVLAQNVGTTHDLLDICLRRA
                     TVQGAQHVFQHVVPQEGKPVTNQKSSGRCWIFSCLNVMRLPFMKKFNIEEFEFSQSYL
                     FFWDKVERCYFFLNAFVDTAQKKEPEDGRLVQYLLMNPTNDGGQWDMLVNIVEKYGVV
                     PKKCFPESHTTEATRRMNDILNHKMREFCIRLRNLVHSGATKGEISSTQDAMMEEIFR
                     VVCICLGNPPETFTWEYRDKDKNYHKIGPITPLQFYKEHVKPLFNMEDKICFVNDPRP
                     QHKYNKLYTVDYLSNMVGGRKTLYNNQPIDFLKKMVAASIKDGEAVWFGCDVGKHFNG
                     KLGLSDMNVYDHELVFGVSLKNMNKAERLAFGESLMTHAMTFTAVSEKDNQEGTFVKW
                     RVENSWGEDHGHKGYLCMTDEWFSEYVYEVVVDKKHVPEEVLAVLEQEPIVLPAWDPM
                     GALAE"
     exon            239..436
                     /gene="Blmh"
                     /gene_synonym="Bh; Bmh"
                     /inference="alignment:Splign:2.1.0"
     exon            437..546
                     /gene="Blmh"
                     /gene_synonym="Bh; Bmh"
                     /inference="alignment:Splign:2.1.0"
     exon            547..688
                     /gene="Blmh"
                     /gene_synonym="Bh; Bmh"
                     /inference="alignment:Splign:2.1.0"
     exon            689..777
                     /gene="Blmh"
                     /gene_synonym="Bh; Bmh"
                     /inference="alignment:Splign:2.1.0"
     exon            778..870
                     /gene="Blmh"
                     /gene_synonym="Bh; Bmh"
                     /inference="alignment:Splign:2.1.0"
     exon            871..1026
                     /gene="Blmh"
                     /gene_synonym="Bh; Bmh"
                     /inference="alignment:Splign:2.1.0"
     exon            1027..1185
                     /gene="Blmh"
                     /gene_synonym="Bh; Bmh"
                     /inference="alignment:Splign:2.1.0"
     exon            1186..1253
                     /gene="Blmh"
                     /gene_synonym="Bh; Bmh"
                     /inference="alignment:Splign:2.1.0"
     exon            1254..1371
                     /gene="Blmh"
                     /gene_synonym="Bh; Bmh"
                     /inference="alignment:Splign:2.1.0"
     exon            1372..1441
                     /gene="Blmh"
                     /gene_synonym="Bh; Bmh"
                     /inference="alignment:Splign:2.1.0"
     exon            1442..2355
                     /gene="Blmh"
                     /gene_synonym="Bh; Bmh"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2322..2327
                     /regulatory_class="polyA_signal_sequence"
                     /gene="Blmh"
                     /gene_synonym="Bh; Bmh"
                     /note="hexamer: AATAAA"
     polyA_site      2343
                     /gene="Blmh"
                     /gene_synonym="Bh; Bmh"
                     /note="major polyA site"
ORIGIN      
        1 gggcggggct agccccgatg gcgctgactc agcaacgcga ggggggagtt ttgtccctcc
       61 gcggaccccg tttctctcgg ccaccattga gcgggtttcc ttcttccggc gcttagggtg
      121 cgagaaccag gtccggccag ctaggcagcg gactgtagtg taaccccaga gctcacctga
      181 aaaccctgaa aactaacgtt tcctccacga agcagtttgg gcgccatgaa caacgcagga
      241 ctaaattcgg agaaggtatc tgctttgatc cagaaactaa attctgaccc tcagttcgta
      301 cttgcccaga atgtcgggac cacccacgat ctgctggaca tatgtctgag gagggccacg
      361 gtccagggtg ctcagcatgt gtttcaacac gttgtgcctc aggaaggcaa gccagtcacc
      421 aaccagaaga gctctggacg atgctggatc ttttcttgtt tgaatgttat gagacttcca
      481 ttcatgaaaa aatttaacat tgaagaattt gagtttagtc aatcttacct gtttttttgg
      541 gacaaggttg aacgctgtta tttcttcttg aatgcttttg tggacacagc tcagaaaaag
      601 gagcctgaag atgggagact ggtgcagtat ttgcttatga accctacaaa tgatggtgga
      661 cagtgggata tgcttgtcaa tattgttgaa aaatacggtg ttgttcctaa gaaatgcttt
      721 cccgaatcgc atacgacaga ggctaccaga agaatgaatg atattctgaa tcacaagatg
      781 agagaattct gtatacggct tcggaacctg gtacacagtg gagccaccaa aggggagatc
      841 tcatctacac aagatgccat gatggaggag atattcagag tggtgtgcat ctgtttgggc
      901 aacccaccag agaccttcac ctgggagtac cgagacaaag ataaaaatta ccacaagatt
      961 ggccccataa cacccttgca gttttacaag gagcacgtga agccgctctt caatatggaa
     1021 gataagattt gttttgtgaa tgacccacgg ccccagcaca agtacaataa attgtacaca
     1081 gtagactact tgagcaatat ggttggaggg agaaaaacgc tgtataacaa ccagcccatt
     1141 gacttcttga aaaagatggt tgctgcctcc atcaaagatg gagaggctgt gtggtttggc
     1201 tgtgatgttg gaaaacactt caatggcaag ctgggcctca gtgacatgaa tgtctatgac
     1261 catgagttag tgttcggtgt ctccttgaag aacatgaata aagctgagag gttggctttt
     1321 ggtgagtcac tcatgaccca cgccatgacc ttcactgctg tctcagagaa ggataatcag
     1381 gaaggtactt ttgtgaaatg gagagtagag aattcatggg gtgaagacca cggccacaaa
     1441 ggctacctgt gcatgaccga tgagtggttc tcggagtacg tctacgaggt ggtggtggac
     1501 aagaagcatg tcccggaaga ggtgctggct gtgttagagc aggagcccat tgtcctgccg
     1561 gcatgggacc ccatgggggc tttggctgag tgagtgcgtg gactgcctcc tgctctcctc
     1621 ctcccatggg atcggatgga gctgccaagg acagacccgg ggactgaaac caaagttaca
     1681 tggatggctg ttcccacagg atacagtcag actcttgggt ttccagtctc ctccaggaac
     1741 ctctttgaga aaaatgcttt atgctgaaac aaaatattca taaaggaaaa aataaagggg
     1801 aaggatcggg gcatccgttg ctctcctcat ctctgacggc tcaggatctc gtagcatttt
     1861 aattggatgt cattgtcctc tgtcacagtc tttgtgtttg tagtaagacg gagtaagatg
     1921 agcagctgag gtgtacggag aacaaacagt cctgggctcc ttgttcctag agtagattag
     1981 gggagggtta gctaggattt gaactctcaa cgctgcatgc tgcctcacag gtcactgtcc
     2041 ttcctacctg gcagtcgctg aattcaactt ctgccgagtt gtttcctgtg acaggaaagg
     2101 ggaggttgat cggtctgaga tgactccttc tcttcctggt ctgagctgtg gggctccctc
     2161 gggccaggtt aaacggggtt cgagaaaacc ttgtcagggg ctcagctgta atcacgaggg
     2221 tcacccactg agtgctttaa tgtctgtgtg cgttggggtt gggcggggag aggcagcgat
     2281 gctcgttctt tctgataact gatggtgctg agaagctttg gaataaaacc ctttgctaac
     2341 tgagagcaag ccggc
//
